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Surgical treatment has been widely used in patients with refractory slow transit constipation (RSTC). The aim of this network meta-analysis (NMA) was to compare the effects of different colectomies on short-term postoperative complications and quality of life in patients with RSTC. Electronic literature searches were performed in the PubMed, Web of Science, EMBASE, WANFANG DATA, and Cochrane Central Register of controlled trials databases and were searched up to December 2022. Selected to compare the short-term clinical outcomes and quality of life of the treatment of RSTC. A random-effects Bayesian NMA was conducted to assess and rank the effectiveness of different surgical modalities. This study included a total of six non-randomized controlled trials involving 336 subjects. It was found that subtotal colectomy with cecorectal anastomosis (CRA) demonstrated superior effectiveness in several aspects, including reduced hospital stay (MD 0.06; 95% CI [0.02, 1.96]), shorter operative time (MD 4.75; 95% CI [0.28, 14.07]), lower constipation index (MD 0.61; 95% CI [0.04, 1.71]), improved quality of life (MD 4.42; 95% CI [0.48, 4.42]). Additionally, in terms of short-term clinical outcomes, subtotal colectomy with ileosigmoidal anastomosis (SC-ISA) procedure ranked the highest in reducing small bowel obstruction (OR 0.24; 95% CI [0.02, 0.49]), alleviating abdominal pain (OR 0.53; 95% CI [0.05, 1.14]), minimizing abdominal distension (OR 0.33; 95% CI [0.02, 0.65]), and reducing incision infection rates (OR 0.17; 95% CI [0.01, 0.33]). Furthermore, SC-ISA ranked as the best approach in terms of patient satisfaction (OR 0.66; 95% CI [0.02, 1.46]). Based on our research findings, we recommend that CRA be considered as the preferred treatment approach for patients diagnosed with RSTC. [ABSTRACT FROM AUTHOR]

Background and Aim: Programmed death 1 (PD‐1) and programmed death ligand 1 (PD‐L1) inhibitors have transformed the treatment landscape of advanced hepatocellular carcinoma (HCC), but consistent responses are not observed in all patients, and prognostic biomarkers to guide treatment decisions are lacking. We aimed to evaluate the predictive value of PD‐L1 expression in advanced HCC patients treated with PD‐1/PD‐L1 inhibitors. Methods: A comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted. Studies comparing the objective response rate (ORR) and/or disease control rate (DCR) based on the tumor PD‐L1 status of HCC were included. Results: Eleven studies with 1,330 HCC patients treated with PD‐1/PD‐L1 inhibitors were included. Pooled odds ratio (OR) analysis demonstrated a significantly improved ORR in PD‐L1‐positive patients compared with PD‐L1‐negative patients (OR, 1.86, 95% CI, 1.35–2.55). Similar results were observed in the anti‐PD‐1 treatment (p < 0.001) and anti‐PD‐1/PD‐L1 monotherapy (p < 0.001) subgroups. The pooled ORRs in the PD‐L1‐positive and PD‐L1‐negative groups were 26% (95% CI, 20%–32%) and 18% (95% CI, 13%–22%), respectively. For DCR, the pooled OR analysis showed no significant difference between PD‐L1‐positive patients and PD‐L1‐negative patients (66% [95% CI, 55%–76%] vs. 69% [95% CI, 62%–76%]; OR, 0.92, 95% CI, 0.59–1.44). The results were consistent across the drug target and combination treatment subgroups. Conclusion: Positive PD‐L1 expression is associated with a better ORR in advanced HCC patients treated with anti‐PD‐1/PD‐L1‐based therapies. This feature can help to identify HCC patients who will benefit most from PD‐1/PD‐L1 inhibitors. [ABSTRACT FROM AUTHOR]

Introduction: Due to the high recurrence, the HCC prognosis remains poor. Yet, the biomarkers for predicting the recurrence of high‐risk patients are currently lacking. We aimed to develop a signature to predict the recurrence of HCC based on NKG2D ligands. Methods: The multivariate Cox proportional hazards regression was used to select recurrence‐related variables of NKG2D ligands in HCC patients from The Cancer Genome Atlas (TCGA). HCC patients from the OEP000321 dataset and Guilin cohort were used to validate the predictive signature. The mRNA expression of NKG2D ligands was measured by QRT‐PCR. Immunohistochemistry analysis of HCC tissue microarray samples was used to identify the expression of NKG2D ligands. Results: In this study, NKG2D ligands expression in the mRNA and protein level was both abnormally expressed in HCC and associated with recurrence‐free survival (RFS). Then, the recurrence‐related variables of NKG2D ligands in HCC were selected by the multivariate Cox proportional hazards regression. Among the eight NKG2D ligands, MICA (HR = 1.347; 95% CI = 1.012–1.793; p = 0.041), ULBP3 (HR = 0.453; 95% CI = 0.231–0.889; p = 0.021) and ULBP5 (HR = 3.617; 95% CI = 1.819–7.194; p < 0.001) were significantly correlated with RFS in the TCGA‐LIHC cohort. Then, the signature was constructed by the three NKG2D ligands. The predictive effectiveness of this signature was also validated in the OEP000321 dataset and Guilin cohort. Further, HCC patients were classified into low‐risk and high‐risk subgroups by the predictive score. Compared with the low‐risk group, the high‐risk group had poor RFS in both training and validation cohorts. Importantly, compared with the low‐risk patients with the G1‐G2 stage, the levels of infiltrated NK‐activated cells and NKG2D expression were both lower in the high‐risk patients. Conclusions: The signature based on MICA, ULBP3, and ULBP5 could predict HCC recurrence. [ABSTRACT FROM AUTHOR]

Simple Summary: The lack of precision biomarkers hinders the development of individualized immunotherapy for esophageal cancer (ESCA) patients. The activation of WNT signaling has proved to be associated with the primary resistance to immunotherapy. Therefore, our study aims to develop efficient biomarkers based on WNT signaling to guide ESCA immunotherapy. In the TCGA cohort with 196 cases and our BJCH cohort with 95 cases, we successfully constructed an IGFBP1hiWNT3Alo signature and validated its correlation with the poor prognosis of ESCA patients. Moreover, in 2 GEO cohorts with a total of 68 cases and our BJIM cohort with 21 cases, we verified that IGFBP1hiWNT3Alo ESCA patients had a good response and prognosis with immunotherapy. Our findings indicate that the IGFBP1hiWNT3Alo signature was a potential immunotherapeutic biomarker for ESCA. PD-(L)1 inhibitor could improve the survival of locally advanced esophageal cancer (ESCA) patients, but we cannot tailor the treatment to common biomarkers. WNT signaling activation was associated with primary resistance to immunotherapy. In this study, we used our two clinical cohorts (BJCH n = 95, BJIM n = 21) and three public cohorts to evaluate and verify a new immunotherapeutic biomarker based on WNT signaling in ESCA patients. Our findings showed that WNT signaling-related genes stratified TCGA patients into Cluster 1, 2, and 3, among which, Cluster 3 had the worst prognosis. The most up- and down-regulated genes in Cluster 3 were IGFBP1 and WNT3A. Further analysis validated that IGFBP1hiWNT3Alo ESCA patients had significantly poor RFS and OS in the TCGA and BJCH cohorts. Interestingly, IGFBP1hiWNT3Alo patients had a good response and prognosis with immunotherapy in three independent cohorts, exhibiting better predictive value than PD-L1 expression (signature AUC = 0.750; PD-L1 AUC = 0.571). Moreover, IGFBP1hiWNT3Alo patients may benefit more from immunotherapy than standard treatment (p = 0.026). Immune cell infiltration analysis revealed a significant increase in DC infiltration in IGFBP1hiWNT3Alo patients post-immunotherapy (p = 0.022), which may enhance immune response. The IGFBP1hiWNT3Alo signature could predict patients who benefited from PD-(L)1 inhibitor treatment and may serve as a biomarker in ESCA. [ABSTRACT FROM AUTHOR]

Chemokines are a family of cytokines that orchestrate the migration and positioning of immune cells within tissues and are critical for the function of the immune system. CCR2 participates in liver pathology, including acute liver injury, chronic hepatitis, fibrosis/cirrhosis, and tumor progression, by mediating the recruitment of immune cells to inflammation and tumor sites. Although a variety of chemokines have been well studied in various diseases, there is no comprehensive review presenting the roles of all known chemokine ligands of CCR2 (CCL2, CCL7, CCL8, CCL12, CCL13, CCL16, and PSMP) in liver disease, and this review aims to fill this gap. The introduction of each chemokine includes its discovery, its corresponding chemotactic receptors, physiological functions and roles in inflammation and tumors, and its impact on different immune cell subgroups. [ABSTRACT FROM AUTHOR]

Background: Repeat hepatectomy is an important treatment for patients with repeat recurrent hepatocellular carcinoma (HCC). Methods: This study was a multicenter retrospective analysis of 1,135 patients who underwent primary curative liver resection for HCC. One hundred recurrent patients with second hepatectomy were included to develop a nomogram to predict the risk of post-recurrence survival (PRS). Thirty-eight patients in another institution were used to externally validate the nomogram. Univariate and multivariate Cox regression analyses were used to identify independent risk factors of PRS. Discrimination, calibration, and the Kaplan–Meier curves were used to evaluate the model performance. Results: The nomogram was based on variables associated with PRS after HCC recurrence, including the tumor, node, and metastasis (TNM) stage; albumin and aspartate aminotransferase levels at recurrence; tumor size, site, differentiation of recurrences; and time to recurrence (TTR). The discriminative ability of the nomogram, as indicated by the C statistics (0.758 and 0.811 for training cohort and external validation cohorts, respectively), was shown, which was better than that of the TNM staging system (0.609 and 0.609, respectively). The calibration curves showed ideal agreement between the prediction and the real observations. The area under the curves (AUCs) of the training cohort and external validation cohorts were 0.843 and 0.890, respectively. The Kaplan–Meier curve of the established nomogram also performed better than those of both the TNM and the BCLC staging systems. Conclusions: We constructed a nomogram to predict PRS in patients with repeat hepatectomy (RH) after repeat recurrence of HCC. [ABSTRACT FROM AUTHOR]

The crosstalk between the estrogen receptor (ER) and NF-κB signalling pathways has merged in vertebrates and plays a key role in the control of genes involved in inflammation, cell proliferation and apoptosis. However, such crosstalk between the endocrine and immune systems needs to be explored in lower invertebrates. In this study, we identified a 2856-bp homologue of the estrogen receptor from Hong Kong oyster (Ch ER), containing a 5′ untranslated region (UTR) of 234 bp, a 3' UTR of 387 bp, and an open reading frame (ORF) of 2235 bp. We observed that overexpression of Ch ER suppressed Ch Rel-dependent NF-kappaB (NF-κB) activation in the HEK293T (human embryonic kidney 293T) cell line, and depletion of Ch ER in vivo resulted in upregulation of two NF-κB-responsive marker genes, namely, TNF-α and IL-17 , which confirmed its potential role in controlling NF-κB signalling. Furthermore, an EMSA (electrophoretic mobility shift assay) showed that Ch ER could negatively regulate the binding of Ch Rel to NF-κB probe-responsive elements. Serial domain requirement analysis showed that both region C (DNA-binding domain) and region E (ligand-binding domain) of Ch ER were essential for mediating the crosstalk underlying Ch ER-dependent NF-κB suppression. In conclusion, we demonstrate for the first time the negative regulatory role of the ER in NF-κB signalling in oysters, strongly indicating the presence of complex crosstalk between the endocrine and immune systems in lower marine molluscs. ● A gene from Crassostrea Hongkongensis encoding estrogen receptor (ER) was identified. ● Ch ER suppressed the Ch Rel-dependent NF-κB activation. ● Region C (DNA binding domain) and region E (ligand binding domain) of Ch ER are essential to mediate the crosstalk underlying Ch ER-dependent NF-κB suppression [ABSTRACT FROM AUTHOR]

A finite-time control strategy is proposed to solve the problem of position tracking control for a permanent magnet synchronous motor servo system. It can guarantee that the motor's desired position can be tracked in a finite time. Firstly, for the d-axis voltage, a first-order finite-time controller is designed based on the vector control principle. Then, for the q-axis voltage, based on a radial basis function (RBF) neural network, an integral high-order terminal sliding mode controller is designed. Theoretical analysis shows that under the proposed controller, the desired position can be tracked by the motor position in a finite time. Simulation results are given to show that the proposed control method has a strong anti-disturbance ability and a fast convergence performance. [ABSTRACT FROM AUTHOR]

NEMO (NF-κB essential modulator) is one of the important regulatory subunits of the IκB kinase (IκK) complex that controls the activation of the NF-κB signaling pathway. Here, we have identified the homolog of NEMO from the pacific oyster Crassostrea gigas. Cg NEMO harbors the conserved the IκK binding region, NEMO ubiquitin binding domain and Zinc finger domain. In terms of tissue distribution, Cg NEMO is expressed in various tissues with an observed highest expression in the hemocytes. Furthermore, infection by two related Vibrio strains significantly increased Cg NEMO expression in the hemocytes. Cell culture based luciferase reporter assays showed that Cg NEMO activates the NF-κB reporter in a dose-pendent manner. Moreover, Cg NEMO was also found to counter the IkB-dependent inhibitory effect on NF-κB activation, providing a plausible mechanism of NF-κB activation by Cg NEMO. Meanwhile, site-directed mutagenesis demonstrated that the putative ubiquitination site K535 is required for the activation of NF-κB, implying that ubiquitination of NEMO may be involved in regulating its activity. Finally, RNAi mediated knockdown of Cg NEMO in vivo significantly compromised the bacterial induction of key cytokines TNF-α and IL-17, strongly suggesting a role for Cg NEMO in acute immune defense in oyster. In conclusion, this study provides new insights into our understanding about the evolution of NEMO mediated NF-κB activation and the induction of cytokine. Our findings may provide valuable information about diseases control and management in oyster aquaculture. [ABSTRACT FROM AUTHOR]

In vertebrates, embryonic hematopoietic stem and progenitor cells (HSPCs) are derived from a subset of endothelial cells, the hemogenic endothelium (HE), through the endothelial-to-hematopoietic transition (EHT). Notch signaling is essential for HSPC development during embryogenesis across vertebrates. However, whether and how it regulates EHT remains unclear. Here, we show that G protein-coupled receptor 183 (Gpr183) signaling serves as an indispensable switch for HSPC emergence by repressing Notch signaling before the onset of EHT. Inhibition of Gpr183 significantly upregulates Notch signaling and abolishes HSPC emergence. Upon activation by its ligand 7α-25-OHC, Gpr183 recruits β-arrestin1 and the E3 ligase Nedd4 to degrade Notch1 in specified HE cells and then facilitates the subsequent EHT. Importantly, 7α-25-OHC stimulation promotes HSPC emergence in vivo and in vitro, providing an attractive strategy for enhancing the in vitro generation of functional HSPCs. [ABSTRACT FROM AUTHOR]

It is increasingly appreciated that neuroendocrine-immune interactions hold the key to understand the complex immune system. In this study, we explored the role of a reproductive regulation-related hormone, GnRH, in the regulation of immunity in Hong Kong oysters. We found that vibrio bacterial strains injection increased the expression of Ch GnRH. Moreover, Ch GnRH neuropeptide promotes the phagocytic ability and bacterial clearance effect of hemocytes which regarded to be the central immune organ. The content of cAMP after incubation with Ch GnRH peptide was increased, which could be blocked by adenylyl cyclase inhibitor SQ 22,536. Furthermore, the stimulated effect of Ch GnRH peptide on the phagocytosis and bacterial clearance was also blocked by SQ 22,536, H89 and enzastaurin, strongly demonstrating that cAMP dependent PKA and PKC signaling pathway was involved in Ch GnRH mediated immune regulation. In conclusion, this study confirms the presence of neuroendocrine-immune regulatory system in marine invertebrates, which contributes to understand the complexity of oyster immune defense system. • A gene from Crassostrea Hongkongensis encoding GnRH was identified. • Ch GnRH promotes the phagocytic ability and bacterial clearance effect of hemocytes. • cAMP dependent PKA and PKC signaling pathway was involved in Ch GnRH mediated immune regulation. [ABSTRACT FROM AUTHOR]